Role of the G-protein subunit alpha-gustducin in taste cell responses to bitter stimuli.

Many bitter stimuli are believed to bind to specific G-protein-coupled membrane receptors on taste cells. Despite the compelling evidence for its pivotal role in bitter taste sensation, a direct involvement of the G-protein subunit alpha-gustducin in bitter taste transduction in taste cells has not been demonstrated in situ at the cellular level. We recorded activation of taste cells by bitter stimuli using Ca2+ imaging in lingual slices and examined alpha-gustducin immunoreactivity in the same cells. In mice vallate papillae, many, but not all, bitter-responsive cells expressed alpha-gustducin. In agreement with this correlation, the incidence of cells responding to bitter stimuli was reduced by 70% in mutant mice lacking alpha-gustducin. Nevertheless, some taste cells lacking alpha-gustducin responded to bitter stimuli, suggesting that other G-protein alpha subunits are involved. We found that the G-protein alpha subunit Galpha(i2) is present in most bitter-responsive cells and thus may also play a role in bitter taste transduction. The reduced behavioral sensitivity to bitter stimuli in alpha-gustducin knock-out mice thus appears to be the consequence of a reduced number of bitter-activated taste cells, as well as reduced sensitivity.